Purinergic modulation of the immune response to infections

Eberhardt, Natalia; Bergero, Gastón; Mariotta, Yanina L. Mazzocco; Aoki, María Pilar

doi:10.1007/s11302-021-09838-y

Cited by 20 publications

(14 citation statements)

References 190 publications

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“…Purinergic signaling is of increasing interest in many infectious diseases [51][52][53][54][55][56]. We investigated the expression of CD39 and CD73 on bulk and SARS-CoV-2-specific CD4 + T-cells.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence has been generated for the immunomodulatory functions of purinergic signaling in viral infections such as HIV and other infectious diseases [51][52][53][54][55][56]. During inflammation and tissue damage, adenosine triphosphate (ATP) is released to extracellular compartments, and acts as a pro-inflammatory mediator [57][58][59].…”

Section: Cd39 Expression Marks Sars-cov-2-specific Cd4 + T-cells In T...mentioning

confidence: 99%

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High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Cords

Knapp

Woost

et al. 2022

Viruses

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Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145–164) epitope-specific CD4+ T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class II DRB1*11:01 Tetramer analysis. We detected a high and stable SARS-CoV-2 membrane-specific CD4+ T-cell response in both patients, with higher frequencies of virus-specific CD4+ T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4+ T-cell memory phenotype in the B-cell-depleted patient that was skewed towards late differentiated memory T-cells, as well as reduced frequencies of SARS-CoV-2-specific CD4+ T-cells with CD45RA− CXCR5+ PD-1+ circulating T follicular helper cell (cTFH) phenotype. Furthermore, we observed a delayed contraction of CD127− virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4+ T-cells of the patient, but were associated with the inflammation markers IL-6 and CRP. Our findings indicate that, despite B-cell depletion and a lack of B-cell—T-cell interaction, a robust virus-specific CD4+ T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection.

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Section: Discussionmentioning

confidence: 99%

Section: Cd39 Expression Marks Sars-cov-2-specific Cd4 + T-cells In T...mentioning

confidence: 99%

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Cords

Knapp

Woost

et al. 2022

Viruses

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“…Alterations in the expression and frequency of CD39 and CD73 in leukocytes have already been reported during viral infections and seem to contribute to the inflammatory immunopathology of those diseases (14-16). In addition, it has been reported that viral infection and the viral load itself might influence the purinergic signaling in different viral infections (17,18). In COVID-19 patients, specifically, there is evidence that the expression of ectoenzymes is modified in T cell lymphocytes and monocytes (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients

Pietrobon

Andrejew²,

Alberca³

et al. 2022

Front. Immunol.

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Ectonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients’ cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease.

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“…The ATP release from immune and non-immune cells can increase as a response to pathogenic infections, while subsequent activation of P2X7R following ATP binding leads to the modulation of innate/adaptive immune responses [ 93 , 94 ]. For this reason, growing evidence indicates that P2X7R plays an important role in pathogen infection-driven inflammation [ 88 , 95 , 96 ]. The receptor has therefore been described as involved in the host response to various pathogenic infections including viruses, bacteria, fungi, protozoa, and even helminths [ 96 ].…”

Section: P2x7 Receptor Activation In Inflammationmentioning

confidence: 99%

“…The inhibition of P2X7R signalling can also lead to antimycobacterial activities. For instance, P2X7R inhibition with Brilliant blue G (BBG) can prevent the development of a severe form of Micobacterium tuberculosis -driven tuberculosis in mice with experimental advanced pulmonary tuberculosis [ 110 ], while the adoptive transfer of P2X7R KO hematopoietic cells in mice can lead to a reduced pneumonia as well as a lower lung Micobacterium bovis burden in comparison with WT mice [ 95 ]. Furthermore, P2X7R has been reported to be implicated during the Gram-positive bacterial infection responsible for sepsis .…”

Section: P2x7 Receptor Activation In Inflammationmentioning

confidence: 99%

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

Rotondo

Mazziotta

Lanzillotti

et al. 2022

Cancers

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The purinergic P2X7 receptor (P2X7R) is a transmembrane protein whose expression has been related to a variety of cellular processes, while its dysregulation has been linked to inflammation and cancer. P2X7R is expressed in cancer and immune system cell surfaces. ATP plays a key role in numerous metabolic processes due to its abundance in the tumour microenvironment. P2X7R plays an important role in cancer by interacting with ATP. The unusual property of P2X7R is that stimulation with low doses of ATP causes the opening of a permeable channel for sodium, potassium, and calcium ions, whereas sustained stimulation with high doses of ATP favours the formation of a non-selective pore. The latter effect induces a change in intracellular homeostasis that leads to cell death. This evidence suggests that P2X7R has both pro- and anti-tumour proprieties. P2X7R is increasingly recognised as a regulator of inflammation. In this review, we aimed to describe the most relevant characteristics of P2X7R function, activation, and its ligands, while also summarising the role of P2X7R activation in the context of inflammation and cancer. The currently used therapeutic approaches and clinical trials of P2X7R modulators are also described.

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Purinergic modulation of the immune response to infections

Cited by 20 publications

References 190 publications

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

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